{
  "abstract": "The RAF-MEK-ERK signaling pathway plays a central role in cancer development and progression and represents an important target for anticancer drug discovery. Simultaneous targeting of components of this pathway may therefore represent a promising strategy for cancer treatment. A quantitative structure-activity relationship (QSAR) model was developed using multiple linear regression (MLR). The QSAR model showed satisfactory predictive performance based on complementary internal and external validation metrics. The selected molecular descriptors were used to guide the structural modification of substituents, resulting in higher predicted activity. Accordingly, ten new molecules were designed through strategic substituent modifications. Synthetic routes for these compounds were also proposed based on reported literature procedures. Molecular docking, molecular dynamics (MD) simulations, and Petra, Osiris, and Molinspiration (POM) analyses supported the prioritization of Pred 9 and Pred 10 as computationally designed candidates for further investigation. In silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated that Pred 9 and Pred 10 may exhibit favorable pharmacokinetic properties. Overall, the results support the consideration of these compounds for experimental synthesis and biological evaluation. However, Pred 9 and Pred 10 have not yet been synthesized or experimentally evaluated for MEK1 inhibition or anticancer activity.",
  "abstract_shown": true,
  "affiliations": [
    "LIMAS Laboratory, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.",
    "Engineering Laboratory of Organometallic, Molecular Materials, and Environment (LIMOME). Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.",
    "Physical-Chemical Laboratory of Materials, Natural Substances and the Environment (LAMSE), Department of Chemistry, Faculty of Sciences, Techniques of Tangier-University Abdelmalek Essaadi, Tangier, Morocco.",
    "Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India.",
    "Laboratory of Analytical and Molecular Chemistry, Faculty of Sciences Ben M'Sik, Hassan II University of Casablanca, Casablanca, Morocco.",
    "Department of Chemistry, College of Science, United Arab Emirates University, Al Ain, United Arab Emirates."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mohammed Er-Rajy"
    },
    {
      "affs": [
        0
      ],
      "name": "Mohamed El Fadili"
    },
    {
      "affs": [
        0
      ],
      "name": "Hanane Etabti",
      "orcid": "0000-0001-5509-8007"
    },
    {
      "affs": [
        1
      ],
      "name": "Arzine Aziz"
    },
    {
      "affs": [
        2
      ],
      "name": "Fatimazohra Lenda"
    },
    {
      "affs": [
        3
      ],
      "name": "Somdutt Mujwar"
    },
    {
      "affs": [
        4
      ],
      "name": "Samir Chtita"
    },
    {
      "affs": [
        5
      ],
      "name": "Abdelouahid Samadi"
    },
    {
      "affs": [
        0
      ],
      "name": "Menana Elhallaoui"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fg9rpzwwdv9dz.bib",
  "cited_by": 0,
  "doi": "10.3389/fbinf.2026.1964610",
  "fulltext_url": "https://europepmc.org/articles/PMC13713695",
  "id": "fg9rpzwwdv9dz",
  "issns": [
    "2673-7647"
  ],
  "landing_url": "https://europepmc.org/article/MED/42953008",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "1703|Computational Drug Discovery Methods"
    ]
  ],
  "openalex": "W7221825974",
  "pdf_url": "https://europepmc.org/articles/PMC13713695?pdf=render",
  "pmcid": "PMC13713695",
  "pmid": "42953008",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fg9rpzwwdv9dz.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T00:20:41Z",
      "native_id": "MED:42953008",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42953008"
    },
    {
      "first_seen": "2026-10-31T12:24:12Z",
      "native_id": "PMC13713695",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fbinf.2026.1964610"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Genomics and Phylogenetic Studies",
      "subfield": "molecular-biology"
    }
  ],
  "title": "In silico design of novel indolinone-based anticancer agents and proposal of synthetic routes.",
  "title_text": "In silico design of novel indolinone-based anticancer agents and proposal of synthetic routes.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:21:19Z",
  "url": "https://research.draconitic.com/paper/fg9rpzwwdv9dz",
  "venue": "Frontiers in bioinformatics",
  "versions": []
}